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46 Cards in this Set
- Front
- Back
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Immunodeficiency diseases:
Associated with ... infections Deficiencies have been found in both the innate and adaptive immune systems Inherited defects commonly account for immunodeficiency diseases Diagnostic tests include: -Routine ... work-up -Flow ... -Assessment of ... and ... function -ELISA |
recurrent
blood cytometry phagocyte T cell |
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Inherited Immunodeficiency Diseases:
-Due to ... mutations in single gene -Mutation observed in ... or ... -Symptoms dependent on the ... of the protein or glycoprotein in the immune response -Severe disease seen when mutated gene codes of a protein of ... function -Less severe disease seen when mutated gene is a member of ... family |
recessive
protein or glycoprotein role unique multigene |
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Recessive mutations in single gene:
children who inherit defective alleles from both parents are ... -individuals who inherit single defective allele are called ... and can pass the allele to their children -recessive defects found in genes on the X chromosome tend to affect only ... children -inheritance of one defective copy of an X-linked gene is sufficient to cause disease in a male |
immunodeficient
carriers male |
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Mutations occur in a particular protein or glycoprotein:
symptoms dependent on the role of the component in the immune response severe disease result from ... gene that encodes for a protein with a unique function less severe disease states observed when mutation in gene that is a member of ... family -other family members can compensate for the defective gene |
loss-of-function
multigene |
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Deficiencies in the Innate Immunity:
... -Increased susceptibility to extracellular bacteria and fungi ... -Increased susceptibility to extracellular bacteria, especially Neisseria species ... -Increased susceptibility viral infection, especially Herpes simplex |
Phagocytes
Complement Natural killer cells |
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Defects in Phagocytes:
-Phagocyte activity impaired -Decrease ability to ... |
clear infections
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1. ... deficiency
-defect in the common β subunit of leukocytes integrin -integrin needed for extravasation of phagocytes into infected tissue |
Leukocyte adhesion
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2. ... disease
mutations affect any four of the proteins of the NADPH oxidase system unable to produce the superoxide radical O2- resulting in a defective oxidative chronic infections -often lead to granuloma formation |
Chronic granulomatous
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3. ... deficiency
-defect in ... -defective respiratory burst -impaired intracellular pathogen killing |
Glucose-6-phosphate dehydrogenase (G6PD)
G6PD |
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4. ... deficiency
-defect in ... in neutrophil granules and macrophage lysosomes -impaired production of toxic oxygen species -impaired intracellular pathogen killing |
Myeloperoxidase
myeloperoxidase |
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5. ... syndrome
-defect in vesicle fusion -impaired phagocytosis due to the inability to fuse endosomes to lysosomes to form phagosomes |
Chediak-Higashi
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Deficiencies in complement pathways:
Deficiencies in ..., ..., and ... Elimination of immune complexes. Attachment of complement to antibodies bound to antigen (immune complex) -allows for destruction and clearance of the immune complexes Deficiencies in factor ... and ... -susceptibility to extracellular pathogens, particularly pyogenic bacteria Deficiencies in ... -associated with a wide range of pyogenic bacteria -decrease in opsonization and phagocytosis of bacteria -sometimes lead to immune complex disease Deficiencies in ... -result in susceptibility to infection by Neisseria species ONLY |
C1, C4 and C2
D and P C3 MAC components |
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What is this?
Genetically and clinically heterogeneous group of disorder of the cellular and humoral immune function Leads to severe T and B cell dysfunction -B cell defects manifest later than T cell defect Patients present with recurrent persistent infection by opportunistic organisms |
Severe Combined Immunodeficiency (SCID)
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Severe Combined Immunodeficiency Syndrome (SCID):
occurs in a approximately 1 in 100,000 births primary immunodeficiency diseases caused by a number of molecular defects that lead to severe compromise in the number and function of ... cells, ... cells, and ... cells common endpoint of all forms of SCID is lack of ... and ... cell function -B cell defects manifest later than T cell defects -maternal IgG provides initial protection for infants without treatment, most children will succumb to severe infections and death by age 2 years |
T
B occasionally natural killer (NK) T- and B- |
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Deficiencies in T-cell function:
-affect all aspects of ... immunity -depress the immune systems ability to respond to pathogen -persistent, recurrent ... with a broad range of host |
adaptive
infections |
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Deficiencies in B-cell function:
-lack of ... production -infections caused by extracellular ... bacteria -polysaccharide capsules -resistant to phagocytosis |
antibody
pyogenic |
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What are these?
1. T-, B+, NK- 2. T-, B+, NK+ 3. T-, B-, NK+ |
Lymphocyte phenotypes observed in SCID
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Two Main Classes of SCID:
... cell function is always impaired in SCID Based on whether B cell function is directly impaired by molecular defect -B lymphocyte positive (+) -B lymphocytes negative (-) May also observe absence of natural killer cells (+/-)-derived from a common lymphoid progenitor Etiologies of SCID classified according to the corresponding phenotypic lymphocyte profile |
T
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Clincal presentation of SCID:
Most patients present around ... months of age with life threatening, recurrent infections Abnormal clinical findings usually due to ..., not the immunodeficiencies -Failure to thrive -Dehydration -Fever -No lymphadenopathy |
3
infection |
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Clinical presentation :
life-threatening syndrome of recurrent infections, diarrhea, dermatitis, and failure to thrive. most patients present before age 3 months with unusually severe and frequent infections by common or ... pathogens pediatric emergency since survival depends upon expeditious stem cell reconstitution, usually by bone marrow transplantation (BMT). two forms of SCID have been successfully treated with gene therapy -X-linked SCID (XL-SCID) -adenosine deaminase (ADA)–deficient SCID |
opportunistic
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Commonly observed pathogens in SCID:
-Pneumocystis carinii pneumonia -Atypical mycobacterium -Herpes viruses -Candidiasis and other systemic ... infections -Crytosporidium -Pneumococcus and other common ... |
fungal
bacteria |
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... SCID
Accounts for ~50% of SCID cases T-, B+, NK- phenotype Results from a mutation in the IL-2Rγ chain |
X-linked
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... SCID
Account for remaining cases of SCID T-, B+, NK+ and T-, B-, NK+ phenotype Variety of molecular disorders |
Autosomal recessive
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X-linked SCID (XL-SCID):
Most ... form of SCID T-, B+, NK- -Variable levels of B lymphocytes that do not produce functional ... Mutation in the common ... chain of the interleukin receptors (IL-2R, IL-4R, IL-7R, IL-9R and IL-15R) |
common
antibodies γ |
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X-linked SCID:
-... (abnormally low number of lymphocytes in the blood) -absence to near absence of ... cells (CD3+) and ... cells (CD16+) |
lymphopenia
T NK |
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Mutation in the common γ chain of the interleukin receptors:
... - loss of lymphocyte proliferation signal ... - inability of B cells to class switch ... - loss of TCR rearrangement ... - loss of anti-apoptotic signal resulting in loss of T-cell selection in thymus ... - ablation of NK cell development |
IL-2R
IL-4R IL-7R IL-9R IL-15R |
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Autosomal Recessive SCID:
... Deficiency Defects in the ... salvage pathway -Adenosine deaminase deficiency -Purine nucleoside phosphorylase deficiency ... syndrome -MHC class I deficiency -MHC class II deficiency |
JAK3
purine Bare lymphocyte |
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JAK3 deficiency:
-Accounts for ~30% of SCID cases -T-, B+, NK- phenotype -JAK3 is a protein tyrosine kinase that associates with the common ... chain of the interleukin receptor -Same clinical manifestations as XL-SCID |
γ
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Defects in the Purine Salvage Pathway:
Enzyme deficiencies in the purine salvage pathways ... deficiency -T-, B-, NK- phenotype ... deficiency -T-, B+, NK- phenotype Recurrent viral, bacterial, fungal, mycobacterial and protozoal infections ... deficits |
Adenosine deaminase (ADA)
Purine nucleoside phosphorylase (PNP) Neurological |
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Defects in the Purine Salvage Pathway:
-enzyme deficiencies in the purine salvage pathways -accumulation of ... metabolites |
toxic
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Adenosine deaminase (ADA) deficiency:
-accumulation of..., ... and ... block T-, B-, and NK-cell development -lymphopenia -decreased or absent ... |
ADP
ATP GTP antibodies |
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Purine nucleoside phosphorylase (PNP) deficiency:
-accumulation of ... and ... lead to selective destruction of thymocytes -lymphopenia -normal B cell levels, deficient in antibodies |
dATP
dGTP |
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Bare Lymphocyte Syndrome:
MHC class I deficiency -T-, B+, NK+ -Defect in either gene encoding the ... peptide transporter -Selective loss of ... T cells MHC class II deficiency -T-, B+, NK+ -Defects in the ... regulators of all HLA class II loci -Selective loss of ... T cells |
TAP
CD8 transcriptional CD4 |
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Bare Lymphocyte Syndrome
MHC class I deficiency: -defect in either gene encoding the ... peptide transporter -impedes peptide binding to HLA class I molecules -absence of ... T cells -no ... T-cell responses to intracellular infections |
TAP
CD8 cytotoxic |
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Bare Lymphocyte Syndrome
MHC class II deficiency: defect in transcriptional regulators of all HLA class II loci; no HLA class II expression -MHC class II transactivator (CIITA) -RFXANK, RFX5 and RFXAP are components of the RFX complex that is involved in controlling transcription absence of ... T cells compromises all compartments of the ... immune response |
CD4
adaptive |
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What syndrome is this?
-Thymic hypoplasia or asplasia leading to defective T-cell function -Contiguous deletion of 22q11.21 through 22q11.23 -Recurrent infections begin soon after birth -Degree of immunodeficiency varies considerably -Complete syndrome is fatal without treatment |
DiGeorge Syndrome
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DiGeorge’s syndrome:
-... and parathyroid hypoplasia leading to T-cell immunodeficiency and hypoparathyroidism -result a gene deletion in the DiGeorge chromosomal region at 22qll (90% of cases) -partial, in which some T-cell function ..., or complete, in which T-cell function is ... -complete DiGeorge syndrome is ... without treatment |
thymic
exists absent fatal |
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Clinical presentation of DiGeorge syndrome:
- recurrent ... begin soon after birth, -degree of immunodeficiency varies considerably, -T-cell function may improve spontaneously -characteristic facies: hypertelorism, micrognathia, ‘fish-mouth’ appearance and low set ears |
infections
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Wiskott-Aldrich Syndrome:
-... recessive disorder -Defect in the Wiskott-Aldrich syndrome protein (WASp) -WASp binds a small G protein known to regulate the ... cytoskeleton -Problems clearing with encapsulated organisms and viral infections |
X-linked
actin |
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Wiskott-Aldrich Syndrome:
-defect due to mutation in the ... -WASp bind Cdc42, a small G protein known to regulate the organization of the actin cytoskeleton -reorganization of the actin cytoskeleton important in the formation of the ... synapse -lack of functional T ... cells; B-cell responses against polysaccharide coating of pathogens -impairment of ... response Clinical presentation -deficits in growth -skin problems (eczema and purpura) -infections of the head, neck and pulmonary system -higher rate of malignancies -neurological problems |
WASp
immunological helper CTL |
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What syndrome is this?
-X-linked recessive trait -Mutation occurs in the gene that codes for CD40 ligand -Virtually no production of specific antibodies against TD antigens -Abnormally high levels of IgM and low levels of IgG, IgA and IgE -High susceptibility of pyogenic bacteria |
X-linked Hyper IgM Syndrome
(Hyperimmunoglobulin M) |
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X-linked hyper IgM syndrome:
-mutation in the gene that codes for ... increased susceptibility to a wide variety of bacteria, viruses, fungi and parasites -increased risk of developing ... disorders and malignancies |
CD40L
autoimmune |
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CD40L:
required for ... of T lymphocytes and macrophage defect in CD40L results in T-cell effector function -diminishes T-cell driven immunoglobulin class switch by B cells -diminishes macrophage activation defect in CD40L results in macrophage effector function -impairs ... response -marked decrease in neutrophils |
maturation
inflammatory |
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What is this?
-Mutation in the btk gene -B cells never develop past pre-B cell stage |
X-linked agammaglobulinemia
(Bruton’s Syndrome) |
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X-linked agammaglobulinemia (Bruton’s Syndrome):
X-linked genetic trait mutation in the protein tyrosine kinase ... -failure to develop mature B cell -btk important in ... signaling during B cell development -necessary for the proliferation and differentiation of pre-B cells Clinical manifestations -pneumonias -severe, recurrent sinopulmonary infections |
btk (Bruton’s tyrosine kinase)
intracellular |
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Pathophysiology due to lack of mature B cells:
lacking ... tissues -poorly developed germinal centers -peripheral lymph nodes and MALT poorly formed fail to develop ... cells |
lymphoid
plasma |
